[go: up one dir, main page]

WO2010094745A1 - Hydrolysat de crocine - Google Patents

Hydrolysat de crocine Download PDF

Info

Publication number
WO2010094745A1
WO2010094745A1 PCT/EP2010/052064 EP2010052064W WO2010094745A1 WO 2010094745 A1 WO2010094745 A1 WO 2010094745A1 EP 2010052064 W EP2010052064 W EP 2010052064W WO 2010094745 A1 WO2010094745 A1 WO 2010094745A1
Authority
WO
WIPO (PCT)
Prior art keywords
crocetin
crocin
monoester
composition according
weight
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2010/052064
Other languages
English (en)
Inventor
Thomas Eidenberger
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Omnica GmbH
Original Assignee
Omnica GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Omnica GmbH filed Critical Omnica GmbH
Priority to CN201080008377.1A priority Critical patent/CN102802636B/zh
Publication of WO2010094745A1 publication Critical patent/WO2010094745A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/74—Rubiaceae (Madder family)
    • A61K36/744—Gardenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/602—Glycosides, e.g. rutin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to a composition comprising an increased amount of crocetin monoester relative to a naturally occurring amount, which is derived from the hydro lysate of a plant material containing crocin or derivatives thereof.
  • the present invention also provides a method to hydrolyze crocin existing in a plant extract, and further relates to its use.
  • crocin/crocetin As a bright yellow color, crocin/crocetin has been in use for over a thousand years. Usually the colorants are extracted from dried saffron stigma or from the dried fruits of gardenia.
  • Saffron is obtained by drying the stigmas from the flower of Crocus sativus L., whose cultivation probably began during prehistoric Greek times. About 200 stigmas are required to obtain 1 g of colorant.
  • the basic components of saffron, which are responsible for its strong yellow-red color, are cis- and trans-crocins, a family of water-soluble carotenoids.
  • Saffron (Crocus sativus) is not a vegetable, although in some areas of the world the corms of various crocus species are eaten by local peasants. Saffron is one of the most expensive spices on the earth, which has a pleasant spicy, pungent, bitter taste and a tenacious odor. Fortunately, small quantities of saffron go a long way in terms of flavoring. Besides being steeped in tea, it is used for seasoning many foods such as fancy rolls, biscuits, rice, and fish. The slender dried flower stigmas of the saffron constitute the true saffron of commerce. Both of the wholesale price and the retail price are expensive in the marketplace, but saffron has always been popular as a yellowish orange natural dyestuff.
  • Gardenia ⁇ Gardenia jasminoides is another prevailing plant being used for yellow dye.
  • Gardenia has also been used in Japan and China as herbal drugs for their antiphlogistic, diuretic, antipyretic, haemostatic, and cholagogic effects, and can be used to treat contusions.
  • a paste of the herb with flour and wine is used as a poultice on twists, sprains, strains, bruises, and abscesses; very effective in injuries to tendons, ligaments, joints and muscles.
  • it is an important crude drug in traditional Asian medical prescriptions, which have sedative, antipyretic, diuretic, choleretic, and anti-inflammatory effects.
  • Gardenia yellow has been listed in The Japanese Pharmacopoeia as crude drug.
  • Chinese medicine it is considered to have anti-inflammatory, antipyretic, astringent, and haemostatic functions as well as use in the treatment of mastitis. It is also used for irritation, sore and swollen eyes and
  • Gardenia yellow is a yellowish food colorant and a member of the carotenoid family. Its principal pigments are crocin/crocetin derivatives. Gardenia yellow is obtained by extraction with water or ethanol from the fruit of Gardenia. The main component of gardenia yellow is crocin, which is now generally used as a natural yellow pigment. It is very soluble in water compared to other carotenoids. Gardenia yellow is listed in the list of existing food additives in Japan. For example, gardenia yellow pigment has been used as food colorant for Japanese traditional foods, such as ohan (yellow rice colored with gardenia fruit) and kuri-kanroni (yellow chestnuts colored with gardenia fruit and soaked in syrup).
  • ohan yellow rice colored with gardenia fruit
  • kuri-kanroni yellow chestnuts colored with gardenia fruit and soaked in syrup.
  • Crocetin is a natural carotenoid dicarboxylic acid (8,8'-Diapo- ⁇ , ⁇ -carotenedioic acid), which is a brick red crystal with a melting point of 285 °C .
  • crocetin is a polyene di-carboxylic acid (8,8'-diapocarotene-8,8'-diolic acid), whose central unit consists of seven conjugated double bonds and four chain methyl groups.
  • end-groups (carboxyl groups) of crocetin are esterified with glucose or gentiobiose, di-esters of crocetin are produced which can have two equal or different end-groups.
  • crocin is bis (6-O- ⁇ -D-glucopyranosyl- ⁇ -D-glucopyranosyl) ester, ⁇ -crocin, or di-gentiobiose ester of crocetin, having a chemical structure as shown below:
  • crocin also includes natural carotenoids where the sugar moiety is not limited to digentiobiose, and can be defined as a diester formed as the condensation product of any saccharide and the dicarboxylic acid crocetin. This is shown below:
  • R is any sugar residue and each R, independently, can be the same or different.
  • the chemical structure of crocetin is shown as below,
  • Crocetin which is the central core of crocin, and is also the compound responsible for the color of saffron.
  • Crocetin is commercially obtained by hydro lyzing crocin to remove digentiobiose of crocin.
  • Crocin has been shown to be a potent antioxidant, as well as being useful for anti-depression, cancer prevention, enhancing mental function, lowering high cholesterol, and/or inflammation prevention. Crocin, crocetin and its derivatives have also been shown to be able to stimulate bile secretion significantly, being useful to improve many conditions.
  • a saffron multi-glycoside tablet has been approved as a novel oral drug for the treatment of coronary heart disease and angina. This drug product consists of a series of components extracted from saffron, among which crocin is established as the main effective ingredient and the standard control.
  • Crocin is a unique water-soluble carotenoid, which has attracted much research attention for its extensive pharmacological effects. Current research provides that crocin has a big molecular structure that is unsuitable to be absorbed in vivo. It was also found that crocin was not absorbed after oral administration to animals and healthy volunteers (Phytomedicine 14 (2007) 633-36).
  • Crocetin is recognized as one of the active metabolites of crocin in the body, but the increase of crocetin was not significant after repeated oral dose, which indicates that crocetin was rapidly eliminated without accumulation in the body.
  • One possible reason might be that crocetin is insoluble in water. Low solubility in water limits many practical applications in food, beverage, drug or nutraceuticals, which also result in reduced bioavailability in vivo.
  • the present invention surprisingly provides compositions derived from the hydro lysate of a plant material containing crocin or derivatives thereof.
  • the hydro lysates include an increased amount of a crocetin monoester relative to lack of naturally occurring crocetin monoesters found in crocin materials, including extracts.
  • crocetin monoester is crocetin mono glucosyl ester, crocetin mono gentiobiosyl ester or mixtures thereof.
  • compositions have an increased content of crocetin monoester by more than 1 % by weight relative to the amount of monoester that occurs naturally in a plant material that includes crocins. Since crocetin monoesters do not occur in the natural state, there is an increased amount of monoesters in the present hydrolysates.
  • the hydro lysate compositions of the invention can include crocin, crocetin, or other crocetin monoesters wherein the ratio of crocin : monoester : crocetin is from about (0-25):(l-80):(l-60) by weight, or wherein the ratio of crocin : monoester : crocetin is from about (5-15):(10-60):(5-50) by weight, or wherein the ratio of crocin : monoester : crocetin is from about (10-15):(30-50):(30-40) by weight, or even wherein the ratio of crocin : monoester : crocetin is from about 10 to about 40 to about 40 by weight.
  • the plant containing crocin is gardenia or saffron.
  • the present invention also provides a method to prepare the hydrolysate compositions described herein, wherein the hydrolysate is from the hydrolysis under acidic or basic conditions.
  • acidic hydrolysis utilizes HCl, phosphoric acid or oxalic acid.
  • hydrolysates described herein can be used in the comestic, pharmaceutical, nutraceutical or as a dietary supplement.
  • hydrolysates described herein can be used for treating, preventing or improving depression, cancer, gynecological inflammation, atherosclerosis, cardiovascular diseases, Alzheimer's disease, aged-related macular degeneration, hepatitis, cirrhosis, liver cancer lowering high cholesterol, adjusting bile secretion, or enhancing brain health.
  • Figure 1 is an HPLC chromatogram of a hydrolysate of one embodiment of the invention.
  • Figure 2 is an HPLC chromatogram of a hydrolysate of another embodiment of the invention.
  • Figure 3 is an HPLC chromatogram of a hydrolysate of another embodiment of the invention.
  • Figure 4 is an HPLC chromatogram of a hydrolysate of another embodiment of the invention.
  • Figure 5 is an HPLC chromatogram of a hydrolysate of another embodiment of the invention.
  • Figure 6 is a graphical representation of AChE inhibition by hydrolysates of the invention.
  • the present invention is directed to a composition
  • a composition comprising a monoester of crocetin, which is derived from the hydrolysate of plant containing crocin or derivatives thereof.
  • the present invention also provides a method to prepare compositions noted herein by hydrolyzing plant materials containing crocin or the derivatives of crocin.
  • the plant materials containing crocin or derivatives thereof are selected from the group of saffron and gardenia, and includes commercially available saffron.
  • the hydrolysis of the material can be achieved under acidic or basic conditions. In one aspect, the hydrolysis is conducted under acidic aqueous solutions. Under acidic aqueous conditions, crocin or derivatives thereof, undergo hydrolysis and become or partially become a monoester of crocetin or upon further hydrolysis, produces crocetin.
  • R denotes gentiobiosyl, glucosyl, or other possible glucosyls.
  • the monoester of crocetin is crocetin-mono-gentiobioside ester, including trans -type and c ⁇ -type isomers.
  • the monoester of crocetin is crocetin-mono-glucoside ester, including trans-type and c ⁇ -type isomers.
  • the present invention provides compositions enriched in a crocetin monoester.
  • the monoester(s) is present in the isolate by more than 1% by weight, more particularly about 10 % by weight and even more particularly about 40% by weight.
  • the hydrosylates of the invention can be further purified by one or more methods known in the art, such as chromatography, gel chromatography, high performance liquid chromatography, crystallization, affinity chromatography, partition chromatography, distillation and the like. Identification of the particular ester (e.g., crocetin monoester) can be accomplished by methods know to those skilled in the art and include 1 H NMR, chemical degradation, chromatography and spectroscopy, especially homo- and heteronuclear two-dimensional NMR techniques for the characterization of the isolated hydrosylates.
  • the term "purified” or “isolated” is used in reference to the purification and/or isolation of one or more anthocyanins from an anthocyanin extract as described above. Again using conventional methods known in the art, various components of the anthocyanin extract can be separated into purified materials.
  • the anthocyanin(s) of the extract are substantially purified and isolated by techniques known in the art.
  • the purity of the purified compounds is generally at least about 90%, preferably at least about 95%, and most preferably at least about 99% and even more preferably at least about 99.9% (e.g. about 100%) by weight.
  • Crocetin-mono-gentiobioside ester ⁇ trans- or cis- is a main body of the resulting hydrolysate. This monoester plays the leading role in various uses.
  • crocetin-mono-glucoside ester trans- or cis-
  • crocetin-mono-glucoside ester is also useful, although it is not a main ingredient. It is believed, based on the information presented herein, that the monoesters of crocetin provide increased bioavailability of the active component(s) of crocin. This surprising result is noted in the examples below.
  • the ratios of crocetin-mono-gentiobioside ester (trans- or cis-) and/or crocetin-mono-glucoside ester (trans- ox cis-) can be controlled.
  • the final hydrosylate can contain crocetin and/or crocin.
  • crocetin and/or crocin can remain to a certain extent. Removal of crocetin and/or crocin can be achieved by purification methods noted above if so desired.
  • compositions containing crocin, crocetin and/or crocetin monoester(s) are suitable for use to treat various afflictions described herein.
  • Some of the therapeutic activity of the materials may be related to the high degree of unsaturation found in crocin, crocetin and/or the crocetin monoester(s) where seven conjugated double bonds are present.
  • the ratio of crocin : monoester : crocetin is from about (l-25):(l-80):(l-60) on a weigh basis.
  • the ratio of crocin : monoester : crocetin is from about (5-15):(10-60):(5-50) on a weight basis.
  • the ratio of crocin : monoester : crocetin is from about (10-15):(30-50):(30-40) on a weight basis.
  • the ratio of crocin : monoester : crocetin is from about 10 to about 40 to about 40 on a weight basis.
  • the monoester(s) can be crocetin-mono-gentiobioside ester ⁇ trans- or cis-) and/or crocetin-mono -glycoside ester ⁇ trans- ox cis-).
  • the monoester is crocetin-mono-gentiobioside ester ⁇ trans- or cis-).
  • monoesters have increased bioavailability than crocin or crocetin or mixtures thereof.
  • Crocetin is insoluble in water. It is soluble in aqueous alkaline solution, which narrows the potential use of crocetin, such as food colorant. Due to poor water-solubility, crocetin is not easily metabolized in vivo.
  • Crocin has very good water-solubility, and has been referred to as a unique water soluble carotenoid. However, good solubility in an aqueous environment does not provide a physiological advantage to crocin. Due to the molecular weight of the sugar moieties (two gentiobiose groups), crocin has a molecular weight of 976.70 Daltons. As a consequence, it is difficult for such a large molecule to pass through the biomembrane in vivo, which in turn leads to very low bioavailability of crocin.
  • crocin and crocetin are both useful for therapeutic treatments, but poor solubility and low bioavailability are two of their drawbacks.
  • the present invention provides a composition with a high content of monoester(s) of crocetin, which provide increased bioavailability in vivo.
  • crocetin monoesters have only one sugar moiety, which help to maintain water-solubility.
  • one gentiobiose group of crocin is replaced by a carboxyl group, resulting in a change of chemical structure that brings a desirable molecular weight to final product. Therefore, by enhancing water-solubility and lowering molecular weight, the structural disadvantages of crocin/crocetin are circumvented.
  • the hydrolysate compositions of the invention advantageously provide crocetin monoesters that are useful for therapeutic benefits.
  • the present invention provides a product with enhanced properties for treatment of depression, cancer prevention, lowering of high cholesterol, treatment of inflammation both therapeutic and preventative, and other potential pharmaceutical and nutraceutical uses as described herein.
  • the present invention provides that controlled hydrolysis can produce a desired amount of a monoester of crocetin. This can be accomplished by the choice of acid, the concentration of the acid, the temperature range utilized and the length of hydrolysis.
  • hydrolysis under acidic conditions can be achieved.
  • Suitable acids include, for example, mineral acids, such as hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, etc. and organic acids, such as oxalic acid, acetic acid, etc.
  • the hydrolysis reaction temperature can be varied from the room temperature to about
  • Hydrolysis time can be varied according to other reaction conditions. For example heating for a period of from 1 to about 5 hours at a temperature under 70 0 C, is suitable to achieve hydrolysis to monoester(s).
  • compositions of the present invention have increase bioavailability relative to crocin or crocetin. Improved absorption of crocin hydrolysate in vivo enhances the activity of saffron/gardenia plant extract. An equivalent uptake amount of the hydrolysate of the invention produces enhanced effects in contrast to the traditional products of saffron/gardenia. Therefore, the compositions of the present invention are useful in applications of cosmetic, pharmaceutical, nutraceuticals and dietary industries, especially as described below:
  • Antidepressant Saffron has been used in folk medicine as antidepressant. Increased absorption of monoester(s) make the product of the present invention valuable for the treatment of depression.
  • composition enriched in monoester of crocetin of the present invention will be better at lowering high cholesterol of the body.
  • Bile is a complex fluid containing water, electrolytes and a battery of organic molecules including bile acids, cholesterol, phospholipids and bilirubin that flow through the biliary tract into the small intestine.
  • bile acids include bile acids, cholesterol, phospholipids and bilirubin that flow through the biliary tract into the small intestine.
  • Bile contains bile acids, which are critical for digestion and absorption of fats and fat-soluble vitamins in the small intestine. 2. Many waste products, including bilirubin, are eliminated from the body by secretion into bile and elimination in feces.
  • Bile acids are derivatives of cholesterol synthesized in the hepatocyte. Bile acids contain both hydrophobic (lipid soluble) and polar (hydrophilic) faces. Thus bile acids carry out two important functions; one is emulsification of lipid aggregates; emulsification is not digestion per se, but is of importance because it greatly increases the surface area of fat, making it available for digestion by lipases, which cannot access the inside of lipid droplets. The other is solubilization and transport of lipids in an aqueous environment; bile acids are lipid carriers and are able to solubilize many lipids. Bile acids are also critical for transport and absorption of the fat-soluble vitamins.
  • Saffron/gardenia extract can adjust bile secretion significantly and is widely used in Asian countries as a Chinese traditional cholagogic drug.
  • the composition enriched in monoester of crocetin of the present invention is effective on ailments caused with digestion disturbances.
  • the hydrolysates of the invention can be used to treat or prevent liver disease. It is believed that by adjusting bile secretion, the hydrolysates of the invention can treat or prevent various liver diseases, including hepatitis, cirrhosis as well as liver cancer, etc.
  • the present invention provides a potent therapeutic for gynecological inflammation.
  • Atherosclerosis is a slow, progressive disease that causes hardening and narrowing of medium to large blood vessels, such as the aorta and the coronary arteries.
  • Some of the risk factors for atherosclerosis include being overweight or obese, having high cholesterol, high blood pressure, and cigarette smoking. The specific cause of the disease remains unknown.
  • Treatment may involve lifestyle changes, medication, certain medical procedures, or a combination of these.
  • Atherosclerosis prevention starts with recognizing the individual's risk factors for the condition, such as high cholesterol, high blood pressure, or diabetes, and then treating and monitoring these conditions.
  • An important component is adopting a healthy lifestyle, which includes following a healthy diet, maintaining a healthy weight, being physically active, and stopping (or not starting) smoking.
  • prevention of atherosclerosis may include taking medication. Therefore, based increased bioavailability of the hydro lysates of the invention, cholesterol can be lowered and in turn atherosclerosis can be treated.
  • Brain health also cognitive health, is a growing concern for people of all ages. Parents are learning about the importance of nutrition for their babies, toddlers and adolescents. Teenagers and adults need to be mentally sharp and focused for school and work. Seniors face conditions such as Alzheimer's and cognitive decline as they age. Substances that inhibit AChE activity are candidates for cognitive health. Therefore, with increased AChE inhibition relative to saffron ⁇ gardenia compositions, the hydrolysate compositions or monoester(s) of the present invention are useful for brain health brain , as a nutraceutical or drug. Cardiovascular diseases:
  • Cardiovascular disease refers to the class of diseases that involve the heart or blood vessels (arteries and veins), and technically refers to any disease that affects the cardiovascular system. Most countries face high and increasing rates of cardiovascular disease. There is therefore increased emphasis on preventing cardiovascular disease by modifying risk factors, such as healthy eating, exercise and avoidance of smoking. The increased bioavailability of the hydro lysate compositions or monoester(s) of the present invention, relative to traditional saffron/gardenia compositions, help to reduce high cholesterol, which plays an important role in treatment or improvement of cardiovascular diseases.
  • the hydro lysates of the invention can be used to treat or prevent age-related macular degeneration (AMD).
  • Age-related macular degeneration is a disease associated with aging that gradually destroys sharp, central vision. Central vision is needed for seeing objects clearly and for common daily tasks such as reading and driving. AMD affects the macula, the part of the eye that allows an individual see fine detail. AMD is already a leading cause of vision loss in Americans 60 years and older.
  • the hydrolysates of the present invention provide the ability to treat, prevent or at least reduce the progress of AMD in an individual.
  • hydro lysate compositions or monoesters of the present invention can help reduce or prevent the spread of cancer.
  • compositions of the invention can be formulated in a conventional manner using one or more physiologically acceptable carriers, diluents, excipients or auxiliaries that facilitate processing of the compositions into useful preparations.
  • compositions of the invention can take a form suitable for virtually any mode of administration, including, for example, oral, buccal, systemic, injection, transdermal, rectal, vaginal, etc., or a form suitable for administration by inhalation or insufflation.
  • Systemic formulations include those designed for administration by injection, e.g., subcutaneous, intravenous, intramuscular, intrathecal or intraperitoneal injection, as well as those designed for transdermal, transmucosal oral or pulmonary administration.
  • Useful injectable preparations include sterile suspensions, solutions or emulsions of the hydrolysis compositions in various vehicles.
  • the compositions can also contain formulating agents, such as suspending, stabilizing and/or dispersing agent.
  • the formulations for injection can be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, and can contain added preservatives.
  • the injectable formulation can be provided in powder form for reconstitution with a suitable vehicle, including but not limited to sterile pyrogen free water, buffer, dextrose solution, etc., before use.
  • a suitable vehicle including but not limited to sterile pyrogen free water, buffer, dextrose solution, etc.
  • the hydro lysate of the present invention can be dried by any art-known technique, such as lyophilization, and reconstituted prior to use.
  • penetrants appropriate to the barrier to be permeated are used in the formulation.
  • penetrants are known in the art.
  • compositions of the invention can take the form of, for example, lozenges, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g., lactose, micro crystalline cellulose or calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulfate).
  • binding agents e.g., pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose
  • fillers e.g., lactose, micro crystalline cellulose or calcium hydrogen phosphate
  • lubricants e.g., magnesium stearate, talc or silica
  • disintegrants
  • Liquid preparations for oral administration can take the form of, for example, elixirs, solutions, syrups or suspensions, or they can be presented as a dry product for constitution with water or other suitable vehicle before use.
  • Such liquid preparations can be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol, or fractionated vegetable oils); and preservatives (e.g., methyl or propyl p hydroxybenzoates or sorbic acid).
  • the preparations can also contain buffer salts, preservatives, flavoring, coloring and sweetening agents as appropriate.
  • Preparations for oral administration can be suitably formulated to give controlled release of the crocetin monoester as is well known.
  • compositions can take the form of tablets or lozenges formulated in conventional manner.
  • the crocetin monoester can be formulated as solutions (for retention enemas) suppositories or ointments containing conventional suppository bases such as cocoa butter or other glycerides.
  • the crocetin monoester of the present invention can be conveniently delivered in the form of an aerosol spray from pressurized packs or a nebulizer with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoro ethane, fluorocarbons, carbon dioxide or other suitable gas.
  • a suitable propellant e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoro ethane, fluorocarbons, carbon dioxide or other suitable gas.
  • the dosage unit can be determined by providing a valve to deliver a metered amount.
  • Capsules and cartridges for use in an inhaler or insufflator can be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.
  • the product of the present invention can be formulated as a depot preparation for administration by implantation or intramuscular injection.
  • the compositions can be formulated with suitable polymeric or hydrophobic materials (e.g., as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, e.g., as a sparingly soluble salt.
  • transdermal delivery systems manufactured as an adhesive disc or patch, which slowly releases the compositions for percutaneous absorption, can be used.
  • permeation enhancers can be used to facilitate transdermal penetration of the stabilized anthocyanin compositions. Suitable transdermal patches are described in the known arts.
  • Liposomes and emulsions are well-known examples of delivery vehicles that can be used to deliver the composition of the present invention.
  • Certain organic solvents such as dimethylsulfoxide (DMSO) can also be employed, although usually at the cost of greater toxicity.
  • DMSO dimethylsulfoxide
  • compositions can, if desired, be presented in a pack or dispenser device, which can contain one or more unit dosage forms containing the compositions.
  • the pack can, for example, comprise metal or plastic foil, such as a blister pack.
  • the pack or dispenser device can be accompanied by instructions for administration.
  • Soft gel or soft gelatin capsules can be prepared, for example, without limitation, by dispersing the formulation in an appropriate vehicle (e.g., rice bran oil, and/or beeswax) to form a high viscosity mixture. This mixture is then encapsulated with a gelatin based film using technology and machinery known to those in the soft gel industry. The capsules so formed are then dried to constant weight.
  • an appropriate vehicle e.g., rice bran oil, and/or beeswax
  • the filling of the soft gelatin capsule is liquid (principally a carrier such as rice bran oil or wheat germ oil and/or beeswax if desired) and can include, apart from the compositions, a hydrophilic matrix.
  • the hydrophilic matrix if present, is a polyethylene glycol having an average molecular weight of from about 200 to 1000.
  • Further ingredients are optionally thickening agents and/or emulsifying agent(s).
  • the present invention provides a composition, derived from the hydro lysate of a plant containing crocin or derivatives thereof, comprising an increased amount of a crocetin monoester relative to naturally occurring crocetin monoesters found in crocin extracts.
  • composition according to paragraph 1 wherein the crocetin monoester is crocetin mono glucosyl ester, crocetin mono gentiobiosyl ester or mixtures thereof.
  • composition according to paragraph 1 or 2 wherein the increased content of crocetin monoester is more than 1% by weight relative to the amount of monoester that occurs naturally.
  • composition according to paragraph 3 further comprising crocin, crocetin, or other crocetin monoesters.
  • a composition according to paragraph 4 wherein the ratio of crocin : monoester : crocetin is from about (0-25):(l-80):(l-60) by weight. 6.
  • composition according to paragraph 6, wherein the ratio of crocin : monoester : crocetin is from about (10-15):(30-50):(30-40) by weight.
  • composition according to paragraph 6 wherein the ratio of crocin : monoester : crocetin is from about 10 to about 40 to about 40 by weight.
  • HPLC analysis was performed with a Agilent 1100 system equipped with a C-18 chromatographic column (75 mm x 4.6 mm).
  • AUV-Vis detector monitored the elution profile at 440 nm wavelength.
  • the mobile phase was a solution consisting of 80% methanol and 20% water which contained 0.2% acetic acid.
  • Crocin 13.11% Monoester: 45.20% Crocetin: 41.69%.
  • Crocin is 25.76%, monoester of crocetin is 39.76% and crocetin is 17.51%.
  • the example provides an increased content of crocetin monoester after hydrolysis and purification.
  • This example focuses on an inhibition of Acetycholinesterase (AChE) by Crocin, monoester of crocetin and Crocetin.
  • AChE Acetycholinesterase
  • Inhibitor solution 10 mg of the corresponding samples were respectively dissolved in 1 ml methanol.
  • Enzyme solution A solution of human acetylcholinesterase containing 70 IU enzyme activity/ml H 2 O was prepared.
  • Substrate solution 115.7 mg acetylthiocholine-iodide was weighed into a 10 ml flask and filled to the mark with H 2 O.
  • Galanthamin.HBr is product No. G 1660 in Sigma product directory, a cholinesterase inhibitor.
  • Figure 6 demonstrates inhibition of AChE activity by various samples.
  • Example 6 Cellular uptake of Crocin and crocetin in CaCo-2 cells
  • CaCo -2 cells were incubated with 10 mg Gardenia extract and 10 mg crocetin/ 100 mL medium.
  • the test compounds were dissolved in methanol and then diluted with incubation medium. Incubations were performed at 37°C for 30, 60 and 120 minutes. At each time point, 3 wells were processed for analysis by collection of the incubation medium and extraction of crocin related esters or crocetin absorbed into the cells.
  • Table 7 provides the content of test solution prior to incubation:
  • DGTC digentobiosyl-(trans)crocetin
  • DGCC digentobiosyl-(cis)crocetin
  • Table 8 provides the corresponding data for the test solution obtained after 120 minutes.
  • Table 9 is a summary for the analysis of the cellular content, indicative for the portion absorbed is shown.
  • Table 9 shows tabulated concentrations of crocetin and crocetin-related compounds in the cells:
  • CaCo-2 cells were cultured in Dulbeccos's Modified Eagle Medium containing 20% fetal bovine serum, 1.2% nonessential amino acids, 0.83 mM L-glutamine, 1.2 % penicillin-streptomycin and 0.1 % mercaptoethanole in an atmosphere of 5% CO 2 and 95% air at 37°C.
  • cells were seeded in 6 well plates at a density of 3*10 5 cells per well and grown in an atmosphere of 5% CO 2 and 95% air at 37°C, 7 to 8 days until confluence was reached.
  • the cells were washed with PBS buffer, incubated with 4 ml medium containing the suspended samples for 30, 60 or 120 minutes.
  • Quantification was performed by external standardization after linear regression analysis.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medical Informatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Cardiology (AREA)
  • Birds (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Molecular Biology (AREA)
  • Diabetes (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)

Abstract

La présente invention concerne une composition dérivée de l'hydrolysat d'une plante contenant de la crocine ou ses dérivés. La composition contient une quantité significative de monoester de crocétine. La présente invention a également pour objet une méthode pour hydrolyser la crocine existant dans un extrait végétal et elle concerne en outre son utilisation.
PCT/EP2010/052064 2009-02-18 2010-02-18 Hydrolysat de crocine Ceased WO2010094745A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201080008377.1A CN102802636B (zh) 2009-02-18 2010-02-18 藏花素水解产物

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US15335709P 2009-02-18 2009-02-18
US61/153,357 2009-02-18
US12/706,959 2010-02-17
US12/706,959 US8569247B2 (en) 2009-02-18 2010-02-17 Hydrolysate of crocin

Publications (1)

Publication Number Publication Date
WO2010094745A1 true WO2010094745A1 (fr) 2010-08-26

Family

ID=42560481

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2010/052064 Ceased WO2010094745A1 (fr) 2009-02-18 2010-02-18 Hydrolysat de crocine

Country Status (4)

Country Link
US (1) US8569247B2 (fr)
JP (1) JP2010195779A (fr)
CN (1) CN102802636B (fr)
WO (1) WO2010094745A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014006023A3 (fr) * 2012-07-02 2014-03-06 Margot Schmitz Préparation pharmaceutique
WO2017182688A1 (fr) * 2016-04-18 2017-10-26 Pharmactive Biotech Products, S.L. Extrait de safran et son utilisation pour prévenir les troubles de l'humeur associés à la dépression
JP2019514916A (ja) * 2016-04-29 2019-06-06 ジナン・ユニバーシティＪｉｎａｎ Ｕｎｉｖｅｒｓｉｔｙ クロシン系化合物及びその用途
JP2021126053A (ja) * 2020-02-12 2021-09-02 石川県公立大学法人 アポカロテノイドの製造方法

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012025229A1 (fr) 2010-08-27 2012-03-01 Persavita Ltd. Composition et procédé de fabrication
GB201014340D0 (en) 2010-08-27 2010-10-13 Piraee Mahmood Nutritional supplement formulation comprising saffron and resveratrol
US9889105B2 (en) 2010-11-02 2018-02-13 U.S. Department Of Veterans Affairs In vivo method for treating, inhibiting, and/or prophylaxis of cancer, such as pancreatic cancer
US10155715B2 (en) 2010-11-02 2018-12-18 The United States Of America As Represented By The Department Of Veterans Affairs Purified crocetin compound and method for treating, inhibiting, and/or prophylaxis of cancer, such as pancreatic cancer
WO2012087434A2 (fr) * 2010-11-05 2012-06-28 Healthypharma, Llc Utilisation d'acide phosphorique
JP5677126B2 (ja) * 2011-02-18 2015-02-25 花王株式会社 チロシナーゼ活性抑制剤及び美白用香粧品
US9211298B2 (en) 2012-11-16 2015-12-15 Song Gao Compositions containing enriched natural crocin and/or crocetin, and their therapeutic or nutraceutical uses
JP6196068B2 (ja) * 2013-05-10 2017-09-13 ハウス食品グループ本社株式会社 クチナシ抽出物を含む眠気覚まし用組成物
TWI507202B (zh) * 2013-08-27 2015-11-11 Univ Nat Taiwan Normal 醫藥組成物於製備不正常多麩醯胺聚集類疾病之藥物上之用途
KR101537584B1 (ko) * 2013-10-08 2015-07-21 안동대학교 산학협력단 혈소판 응집저해 상승효과를 나타내는 제니핀 및 크로신을 유효성분으로 함유하는 혈전성 질환의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품
CN103539657B (zh) * 2013-10-24 2015-04-29 陕西源邦生物技术有限公司 一种栀子来源的藏红花酸的制备方法
US10682385B2 (en) * 2014-01-10 2020-06-16 Aftab Ahmad Saffron treatment method for mammalian maladies
CN105935363B (zh) * 2016-04-29 2017-03-08 暨南大学 组合物、藏红花色素类活性部位及其用途
IT201600111933A1 (it) * 2016-11-07 2018-05-07 Fernando Gabriele Giorgio Tateo Metodo per preparare un concentrato deodorizzato e deamaricato di carotenoidi da zafferano e concentrato cosi’ ottenuto e suo uso
CN108553469A (zh) * 2018-04-28 2018-09-21 广州博济堂医药保健有限公司 西红花酸或其衍生物在制备治疗心衰药物中的用途
CN108403677B (zh) * 2018-05-03 2020-06-05 北京市心肺血管疾病研究所 藏红花素在预防和治疗胸主动脉夹层/主动脉瘤中的应用
CN113993515B (zh) * 2019-12-10 2023-08-29 杭州梦岚瑞思生物科技有限公司 使用藏红花酸治疗实体肿瘤的方法
CN115385788B (zh) * 2022-08-28 2024-03-26 浙江工业大学 一种藏红花酸的无溶剂制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0718194A (ja) * 1993-06-30 1995-01-20 Taishiyoo Technos:Kk クロセチンの製造方法
WO2004078695A1 (fr) * 2003-03-07 2004-09-16 Riken Vitamin Co., Ltd. Procede de purification de la crocetine
ES2238004A1 (es) * 2004-01-23 2005-08-01 Asociacion De Investigacion De La Industria Alimentaria Azafran enriquecido en safranal y procedimiento de obtencion.
CN101225040A (zh) * 2007-01-18 2008-07-23 中国科学院过程工程研究所 一种从栀子中提取制备西红花酸的方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004056201A1 (fr) * 2002-12-19 2004-07-08 Council Of Scientific And Industrial Research Procede de preparation d'un concentre d'arome et de pigments de safran
JP2006335859A (ja) * 2005-06-01 2006-12-14 Riken Vitamin Co Ltd 粉末状クロセチン製剤の製造方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0718194A (ja) * 1993-06-30 1995-01-20 Taishiyoo Technos:Kk クロセチンの製造方法
WO2004078695A1 (fr) * 2003-03-07 2004-09-16 Riken Vitamin Co., Ltd. Procede de purification de la crocetine
ES2238004A1 (es) * 2004-01-23 2005-08-01 Asociacion De Investigacion De La Industria Alimentaria Azafran enriquecido en safranal y procedimiento de obtencion.
CN101225040A (zh) * 2007-01-18 2008-07-23 中国科学院过程工程研究所 一种从栀子中提取制备西红花酸的方法

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
ASAI AKIRA ET AL: "Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 53, no. 18, September 2005 (2005-09-01), pages 7302 - 7306, XP002581301, ISSN: 0021-8561 *
BIOLOGICAL & PHARMACEUTICAL BULLETIN, vol. 28, no. 11, 2005, pages 2106 - 2110
DATABASE WPI Week 199513, Derwent World Patents Index; AN 1995-094010, XP002581296 *
DATABASE WPI Week 200562, Derwent World Patents Index; AN 2005-599391, XP002581297 *
DATABASE WPI Week 200869, Derwent World Patents Index; AN 2008-L75569, XP002581295 *
DUFRESNE CHRISTIANE ET AL: "In vitro formation of crocetin glucosyl esters by Crocus sativus callus extract", PLANTA MEDICA, vol. 63, no. 2, 1997, pages 150 - 151, XP009133076, ISSN: 0032-0943 *
PFISTER S ET AL: "Isolation and structure elucidation of carotenoid-glycosyl esters in Gardenia fruits (Gardenia jasminoides Ellis) and saffron (Crocus sativus Linne)", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 44, no. 9, 1996, pages 2612 - 2615, XP002581298, ISSN: 0021-8561 *
PHYTOMEDICINE, vol. 14, 2007, pages 633 - 36
SOEDA S ET AL: "Pharmacological activities of crocin in saffron", JOURNAL OF NATURAL MEDICINES 200704 JP LNKD- DOI:10.1007/S11418-006-0120-9, vol. 61, no. 2, April 2007 (2007-04-01), pages 102 - 111, XP002581302 *
XI ET AL: "Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following oral administration in rats", PHYTOMEDICINE, GUSTAV FISCHER VERLAG, STUTTGART LNKD- DOI:10.1016/J.PHYMED.2006.11.028, vol. 14, no. 9, 2 August 2007 (2007-08-02), pages 633 - 636, XP022183747, ISSN: 0944-7113 *
ZHANG H ET AL: "Semi-preparative isolation of crocins from saffron (Crocus sativus L.)", CHROMATOGRAPHIA 200406 DE, vol. 59, no. 11-12, June 2004 (2004-06-01), pages 691 - 696, XP002581299, ISSN: 0009-5893 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014006023A3 (fr) * 2012-07-02 2014-03-06 Margot Schmitz Préparation pharmaceutique
WO2017182688A1 (fr) * 2016-04-18 2017-10-26 Pharmactive Biotech Products, S.L. Extrait de safran et son utilisation pour prévenir les troubles de l'humeur associés à la dépression
US10933110B2 (en) 2016-04-18 2021-03-02 Pharmactive Biotech Products, S.L. Saffron extract and its use for the prevention of mood disorders related to depression
JP2019514916A (ja) * 2016-04-29 2019-06-06 ジナン・ユニバーシティＪｉｎａｎ Ｕｎｉｖｅｒｓｉｔｙ クロシン系化合物及びその用途
JP2021126053A (ja) * 2020-02-12 2021-09-02 石川県公立大学法人 アポカロテノイドの製造方法
JP7458046B2 (ja) 2020-02-12 2024-03-29 石川県公立大学法人 アポカロテノイドの製造方法

Also Published As

Publication number Publication date
JP2010195779A (ja) 2010-09-09
CN102802636A (zh) 2012-11-28
US20100210572A1 (en) 2010-08-19
US8569247B2 (en) 2013-10-29
CN102802636B (zh) 2020-09-08

Similar Documents

Publication Publication Date Title
US8569247B2 (en) Hydrolysate of crocin
US9745279B2 (en) Sirtuin activator
KR102038810B1 (ko) 성장 호르몬 분비 촉진제
US20170080040A1 (en) Decoction of olive leaves
JP2010502572A (ja) カロテノイド異性体の安定で生物学的に利用可能な皮膚及び毛髪用組成物
KR101903905B1 (ko) 핑클루비 (Sedeveria Pink Ruby) 추출물을 유효성분으로 포함하는, 항암 또는 항산화용 조성물
KR102154092B1 (ko) 비자 열매 추출물 또는 이의 분획물을 포함하는 항산화 또는 항염증 조성물
KR20150034025A (ko) 항산화 또는 혈당 강하 활성 성분 함량이 증가된 새싹보리 차
KR102044228B1 (ko) 갈색거저리 성충으로부터 항산화 활성을 갖는 화합물을 분리하는 방법
KR101806220B1 (ko) 상추꽃 추출물 또는 분획물을 유효성분으로 함유하는 항산화 또는 항노화용 조성물
KR101755017B1 (ko) 선녀배(Dudleya brittonii) 추출물의 제조방법 및 선녀배 추출물을 유효성분으로 함유하는 항암 또는 항산화용 조성물
JP7014483B1 (ja) テストステロン分泌促進剤
EP4142762B1 (fr) Superaliment pour prolonger la longévité d'un individu
US11173187B2 (en) Concentrated oil-based polyphenol composition and a method of producing the oil-based polyphenol composition
US20240316081A1 (en) Method for Prolonging Half-life of Theanine In Vivo
JP2000247880A (ja) 脂肪分解促進剤
WO2018212147A1 (fr) Agent d'élimination de l'aspect terne de la peau, et agent de maintien ou d'amélioration de la fonction barrière de la peau
JP2025056445A (ja) ミトコンドリア機能向上用剤
KR20230139411A (ko) 시트러스 계열 과일 추출물을 유효성분으로 포함하는 항균용 조성물
WO2020045647A1 (fr) Agent pour supprimer l'augmentation de la glycémie, agent de prévention du diabète et composition alimentaire
KR20030083421A (ko) 홍화잎으로부터 항염증 플라보노이드의 추출방법
WO2015129525A1 (fr) PROMOTEUR DE SYNTHÈSE D'ACIDE HYALURONIQUE, PROMOTEUR D'EXPRESSION D'ARNm DE HAS2, PRODUIT PHARMACEUTIQUE, ALIMENTAIRE OU COSMÉTIQUE AYANT UNE ACTION FAVORISANT LA SYNTHÈSE DE L'ACIDE HYALURONIQUE ET PRODUIT PHARMACEUTIQUE, ALIMENTAIRE OU COSMÉTIQUE AYANT UNE ACTION FAVORISANT L'EXPRESSION D'ARNm DE HAS2
KR20160047732A (ko) 상추꽃 추출물 또는 분획물을 유효성분으로 함유하는 항산화 또는 항노화용 조성물

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 201080008377.1

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10704930

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE